ENST00000462876.5:n.1007-2570A>G

Variant names:

• chr7-116495199-A-G
• rs17138756
• ENST00000462876.5:n.1007-2570A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000462876.5(CAV2):​n.1007-2570A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,170 control chromosomes in the GnomAD database, including 967 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (967 hom., cov: 32)
• Consequence: CAV2 ENST00000462876.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938
• Publications: 7 publications found

Genes affected

CAV2 (HGNC:1528): (caveolin 2) The protein encoded by this gene is a major component of the inner surface of caveolae, small invaginations of the plasma membrane, and is involved in essential cellular functions, including signal transduction, lipid metabolism, cellular growth control and apoptosis. This protein may function as a tumor suppressor. This gene and related family member (CAV1) are located next to each other on chromosome 7, and express colocalizing proteins that form a stable hetero-oligomeric complex. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. Additional isoforms resulting from the use of alternate in-frame translation initiation codons have also been described, and shown to have preferential localization in the cell (PMID:11238462). [provided by RefSeq, May 2011]

CAV2 Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000237813 (HGNC:40129):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV2-DT	NR_188009.1	n.163+4155T>C		intron_variant	Intron 1 of 3
CAV2-DT	NR_188010.1	n.163+4155T>C		intron_variant	Intron 1 of 3
CAV2-DT	NR_188011.1	n.163+4155T>C		intron_variant	Intron 1 of 4
CAV2-DT	NR_188012.1	n.163+4155T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV2	ENST00000462876.5	n.1007-2570A>G		intron_variant	Intron 8 of 13	1
CAV2	ENST00000467035.5	n.753-2570A>G		intron_variant	Intron 6 of 8	1
CAV2	ENST00000472470.5	n.407-2570A>G		intron_variant	Intron 3 of 5	1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15460 AN: 152052 Hom.: 961 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0679

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0844

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15488 AN: 152170 Hom.: 967 Cov.: 32 AF XY: 0.0976 AC XY: 7263 AN XY: 74420

African (AFR) AF: 0.175 AC: 7253 AN: 41486

American (AMR) AF: 0.0677 AC: 1035 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0900 AC: 312 AN: 3468

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.0211 AC: 102 AN: 4830

European-Finnish (FIN) AF: 0.0650 AC: 690 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0844 AC: 5740 AN: 68014

Other (OTH) AF: 0.102 AC: 215 AN: 2100

Alfa AF: 0.0948 Hom.: 2243

Bravo AF: 0.108

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.94

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17138756; hg19: chr7-116135253;